effect of imatinib mesylate and the pharmacokinetics of acetaminophen/paracetamol in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (cml-cp)

Conditions: Chronic Myeloid Leukemia (CML)

Summary: a non-randomized, open-label study to investigate the effects of imatinib mesylate on the pharmacokinetics of acetaminophen/paracetamol in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (cml-cp)


Eligibility criteria:
inclusion criteria: * ability to provide written informed consent prior to participation to the study. * male or female patients ≥ 18 and ≤ 75 years of age * patients with cml-cp within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). fish analysis will not be accepted. * diagnosis of cml in chronic phase with cytogenetic confirmation of philadelphia chromosome of (9;22) translocations and presence of bcr-abl * documented chronic phase cml as defined by: * \< 15% blasts in peripheral blood and bone marrow * \< 30% blasts plus promyelocytes in peripheral blood and bone marrow * \< 20% basophils in the peripheral blood * ≥ 100 x 109/l (≥ 100,000 /mm3) platelets * no evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly * adequate end organ function as defined by: * total bilirubin \< 1.5 x uln * sgot and sgpt \< 2.5 x unl * creatinine \< 1.5 x uln * female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug exclusion criteria: * patients in late chronic phase, accelerated phase, or blastic phase are excluded * patients who have received other investigational agents * patients who received imatinib for any duration prior to study entry * patient received any treatment for cml prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide * patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention * patients who are: * pregnant * breast feeding * of childbearing potential without a negative pregnancy test prior to baseline * male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial * post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential * patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes, chronic renal disease) * patient previously received radiotherapy to ≥ 25% of the bone marrow * patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery * patients with an ecog performance status score ≥ 3 * patients with international normalized ratio (inr) or partial thromboplastin time (ptt) \> 1.5 x iuln, with the exception of patients on treatment with oral anticoagulant * patients with known positivity for human immunodeficiency virus (hiv) * baseline testing for hiv is not required * patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent * patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment * patients who are chronic users of acetaminophen or medications containing acetaminophen. * patients who received acetaminophen or medications containing acetaminophen within 72 hours prior to study entry. other protocol-defined inclusion/exclusion criteria may apply

Keywords: pharmacokinetic sti571 imatinib cml chronic myeloid leukemia philadelphia chromosome acetaminophen